tbuckley/cabot-search huggingface dataset:
Abstract 11350: Arrhythmogenic Mitral Valve Prolaspe and Mitral Annular Disjunction
Authors: Garba Rimamskep Shamaki, Favour Markson, Sheda Monfared Beheshti
Journal: Circulation (2022)

Background: Mitral valve prolapse (MVP) affects about 2-3% of the general population. A small proportion of persons may have arrhythmic symptoms, leading to ventricular arrhythmias and sudden cardiac death (SCD). Mitral annular disjunction is a recently described entity that may be present with MVP or independently. Case: A 55-year-old male patient presented to the hospital with cardiac arrest. He has a history of percutaneous coronary intervention with stenting to left anterior descending (LAD) and right coronary artery (RCA) in 2015. He had ventricular fibrillation (VF) and subsequently arrested and underwent resuscitation. Electrocardiogram (EKG) showed sinus rhythm with prolonged QTc 487msec with no ischemia; echocardiography showed mitral annular disjunction, severe left ventricular global hypokinesis with ejection fraction of 10%. Left heart catheterization revealed nonobstructive moderate coronary artery disease. Right heart catheterization showed a severely reduced cardiac index of 2.1, and he was placed on mechanical support (Impella) for cardiogenic shock. On day 5, repeat echocardiography revealed left ventricular ejection fraction of 60%. Subsequent cardiac magnetic resonance (CMR) showed no evidence of infiltrative diseases but revealed an inferolateral wall scar from previous myocardial infarction and MVP with MAD. An implantable cardiac defibrillator was placed for secondary prevention of SCD. Discussion: The potential etiology of our patient's ventricular fibrillation cardiac arrest may include a scar from previous myocardial infarction or arrhythmogenic MVP with MAD. Myocardial fibrosis arising from MAD may be an origin of ectopic activity and arrhythmia. EKG, echocardiographic, and cardiac magnetic resonance imaging (CMR) are essential in diagnosing arrhythmic MVP and MAD. Young patients with premature ventricular contractions without clear etiology should be evaluated for MAD, and incidental findings of MAD should warrant further investigations, given its arrhythmogenic potential. Conclusion: MVP with MAD is associated with life-threatening arrhythmias. Further studies are required to explore treatment options to reduce the incidence of malignant VAs and SCDs in patients with MVP.
Abstract 12571: Optimal Rate Control Strategy in Patients With Atrial Fibrillation: A Meta-Analysis of Randomized Trials and Multivariable Adjusted Studies
Authors: Pedro Abi-Kair Borges Calomeni, LIS VICTORIA RAVANI CARVALHO, Mateus de Miranda Gauza, Jussara Pereira, Rhanderson Cardoso
Journal: Circulation (2022)

Introduction: Atrial fibrillation (AF) is associated with an increased risk of impaired quality of life, stroke, and mortality. Despite multiple studies, the optimal target for rate control in AF is not definitively known. Methods: We performed a systematic review and meta-analysis comparing the effects of strict rate control (&lt;80 bpm at rest) with a lenient rate control strategy (&lt;110 bpm at rest) in patients with AF. The outcomes analyzed were all-cause mortality, cardiovascular (CV) death and CV hospitalization. A subgroup analysis was also performed in patients with heart failure (HF). PubMed, Scopus and Cochrane Central were searched for randomized controlled trials or observational studies with multivariable analyses adjusting for confounders. Results: Seven studies were included. All studies were either randomized or reported multivariate adjusted hazard ratios. There were 14,154 (59.6%) patients in the strict rate control strategy and 9,606 (40.4%) in the lenient group. AF was reported as paroxysmal in 1,697 (7.3%) patients. All-cause mortality was not statistically different between a strict vs. lenient heart rate control strategy, although there was a tendency towards improvement in the strict control group (HR 1.10; 95% CI 1.00-1.22; p=0.05; Figure 1A). In patients with AF and HF, there was also no significant difference between groups (HR 1.13; 95% CI 0.99-1.30; p=0.08; Figure 1B). Furthermore, CV death (HR 0.91; 95% CI 0.75-1.11) and CV hospitalization (HR 1.01; 95% CI 0.96-1.06) were also not significantly different between the two strategies. Conclusions: There was no significant difference in all-cause mortality between strict and leninent rate control in patients with AF among randomized trials or multivariable adjusted studies. In a subgroup of patients with HF, there was also no significant difference between the two rate control strategies.
Abstract 12336: Genetic Testing in a Population of Patients With End Stage Heart Failure — Too Little, Too Late?
Authors: Maani Z Kamal, Jennifer Kang, Eliot G Peyster, Anjali T Owens, Nosheen Reza
Journal: Circulation (2022)

Introduction: Nonischemic dilated cardiomyopathy (CM) is the most common cause of end stage heart failure (ESHF). Familial/genetic CMs are underdiagnosed CM subtypes, and recognition of these CMs has implications for the treatment of patients and their relatives. We aimed to characterize the screening for familial/genetic CM in a cohort of patients with ESHF due to nonischemic CM. Methods: Single-center, retrospective analysis of patients with nonischemic CM who underwent left ventricular assist device or heart transplantation (LVAD/HT) from 1992-2019. Demographics, clinical characteristics, family history (FHx), and genetic testing results were collected. Results: A total of 248 patients (73 women [29%]) were included. Age at CM diagnosis was 23 years (IQR 20.5, 29.5) for patients with suspected or confirmed familial, genetic, or noncompaction CM versus 44 years (IQR 35, 52) for other nonischemic etiologies (p&lt;0.001). A 3-generation FHx was reported for 23% of patients; 25 (18 men [72%]) underwent genetic testing. Median time between LVAD/HT and genetic testing was 519 days. Five patients underwent genetic testing prior to LVAD/HT. Cascade screening was recommended in 15/25 (75%). Twelve of 25 (48%) had a disease-causing genetic variant identified (Table). Among these 12, median age at CM diagnosis was 25.5 years (IQR 20.5, 35) compared with 40.5 years (IQR 27, 45.5) for those (n=13) who underwent genetic testing but did not have any causative variants identified. Conclusion: In this cohort of patients with ESHF due to nonischemic CM, only 23% had a documented 3-generation FHx, only 10% underwent genetic testing, most patients underwent genetic testing after LVAD/HT, and patients with suspected or confirmed familial/genetic CM presented at significantly younger ages. Our findings highlight opportunities to improve underdiagnosis of familial/genetic CM, especially for those patients who present with advanced HF in the third decade of life.
Abstract 11338: Stimulant Use Precipitates Antidromic Atrioventricular Reentrant Tachycardia While Subsequent Evaluation Reveals Underlying Ebstein Anomaly
Authors: Natalie Dapas, Matthew Nazari, Athanasios Thomaides, Monvadi Srichai-Parsia
Journal: Circulation (2022)

Background: Ebstein anomaly (EA) or congenital atrialization of the right ventricle occurs in 0.005% of the population. Developmental tricuspid valve malformations in EA can establish accessory pathways (APs) in 10-30% of these patients. These APs can lead to atrioventricular reentrant tachycardia (AVRT) with sometimes consequent fatal complications (2.7% if untreated). Case: A healthy 23-year-old woman presented with dyspnea and palpitations after cocaine use. Her initial EKG demonstrated wide complex tachycardia with a HR of 200 bpm and BP of 70/40 mmHg. She received electrical cardioversion and amiodarone. Subsequent EKG demonstrated antidromic AVRT versus pathway-pathway tachycardia ( Figure 1A-B ). TTE demonstrated right ventricular atrialization consistent with EA ( Figure 1D-E ). Dual right anterolateral and mid-septal APs were mapped ( Figure 1F ) and ablated. Conclusion: Antidromic AVRT is a life-threatening, wide complex tachycardia that can be mistaken for ventricular tachycardia, with the potential for catastrophic outcomes if mismanaged. Demonstrative EKG findings reveal the diagnosis ( Figure 1-2 ), while hemodynamic stability guides acute management ( eg , IV procainamide vs cardioversion, Figure 2C ), followed by AP ablation for definitive management. Rapid recognition with evaluation for structural disease (herein as EA) is essential to affording optimal management in AVRT.
Abstract 11104: Percutaneous Embolization of Extensive Collateral Vessels for Hemoptysis in Pulmonary Aspergilloma
Authors: Paulamy Ganguly, Zhihao Zhu, C Huie Lin
Journal: Circulation (2022)

Introduction: Pulmonary aspergillomas form due to fungal colonization in patients with immunocompromise and underlying cavitary lung disease. They can present with hemoptysis due to erosion of pulmonary vessels and formation of collaterals. Arterial embolization of bronchial vessels is considered first line treatment due to effectiveness and minimal invasiveness. We present one patient with need for extensive embolization treatment for persistent hemoptysis. Case: 53yo woman with pulmonary sarcoidosis and bilateral pulmonary aspergilloma presented to our institution for lung transplant evaluation. She had persistent hemoptysis for years after being diagnosed. She previously had bronchial artery embolization at outside hospital but had persistent symptoms severely limiting her functional status. She continued to have active hemoptysis during the admission, including on arrival to procedure. Angiography demonstrated extensive collateral vessels from systemic arterial to pulmonary circulation including several large branches originating from the subclavian arteries, internal mammary arteries and dorsal scapular arteries. There was leak through multiple previously embolized arteries, with active extravasation of contrast. Initial large collaterals were embolized using Medtronic MVP micro-vascular plugs (3Q, 5Q, 7Q) and smaller collaterals from intercostal arteries embolized using Penumbra Ruby Coil. She had improvement following the first procedure, but had persistent hemoptysis requiring repeat procedures to address more collateral and native vessels prior to resolution of symptoms. Conclusions: This patient with bilateral pulmonary aspergilloma had previous unsuccessful coil embolizations and complex collateral vessel system that resulted in severe recurrent bleeds. We successfully treated this patient’s persistent massive hemoptysis after extensive embolizations during multiple challenging procedures.
Abstract 11529: Sociodemographic and Clinical Variables Predict Acute Coronary Syndrome Symptom Knowledge, Attitudes, abd Beliefs in Adults Without Diagnosed Heart Disease
Authors: John R Blakeman, MyoungJin Kim, Marilyn A Prasun
Journal: Circulation (2022)

Introduction: Little research has focused on the acute coronary syndrome (ACS) symptom knowledge, attitudes, and beliefs of younger individuals and those without diagnosed heart disease, even though most ACS events are first-time events, and ACS rates are increasing in the young. Purpose: To identify predictors of ACS symptom knowledge, attitudes, and beliefs in younger people without diagnosed heart disease. Methods: Participants were recruited from social media platforms in fall 2020 and completed an online survey including the ACS Response Index instrument. Multiple linear regressions were run to model ACS symptom knowledge, attitudes, and beliefs as a function of selected demographic and clinical variables that have documented or theoretical importance. Results: A typical participant from the sample (n=765) was 36.4 years old (SD = 16.7), a woman (n=573; 74.9%), white (n=686; 89.7%), and non-Hispanic/Latino (n=706; 92.3%). Hispanic/Latino participants had lower ACS symptom knowledge and attitude scores than non-Hispanic/Latino participants, (β = -.26, t (757) = -7.79, p = .000; β = -1.32, t (755) = -2.86, p = .000, respectively), and white participants had substantially higher ACS symptom attitude scores than non-white, (β = 1.21, t (755) = 3.35, p = .001). Men had lower knowledge scores than women, (β = -6.48, t (757) = -4.41, p = .000). Additionally, participants who reported being taught by a healthcare professional about signs and symptoms of ACS had substantially higher symptom knowledge and attitude scores compared to those who had not, (β = 3.70, t (757) = 3.01, p = .003; β = 2.15, t (755) = 11.68, p = .000, respectively) and so did those who reported exposure to information about these symptoms in the media compared to those who did not, (β = 6.68, t (757) = 4.37, p = .003; β = 1.07, t (755) = 4.58, p = .000, respectively). Other variables, such as use of avoidance coping, self-perceived risk of heart disease, nicotine use, and self-perceived health, also predicted knowledge, attitude, and/or belief scores. Conclusions: Gender, race, and previous exposure to information about ACS symptoms were particularly important predictors of ACS symptom knowledge and attitudes, though others were significant. Additional research is needed in more diverse samples.
Abstract 12450: Identifying Differential Proteins of the Arrhythmogenic Right Ventricular Cardiomyopathy Type 5 Associated Mutation in Transmembrane Protein 43 Ser358Leu by Proteomics and Interaction Studies Using TurboID
Authors: Sandra Ratnavadivel, Nora Klinke, Miriam Bernauer, Heiko Harten, Achim Paululat, Jan Gummert, Hendrik Milting
Journal: Circulation (2022)

Introduction: Transmembrane protein 43 (TMEM43) is localized in the nuclear envelope and endoplasmic reticulum (ER). TMEM43- c.1073C&gt;T, p.S358L leads to a rare fully penetrant type 5 arrhythmogenic right ventricular cardiomyopathy (ARVC5). The molecular pathomechanism of ARVC5 is not well understood. Methods: TurboID cloned to N- and C-terminal of TMEM43 WT and p.S358L were transfected in HEK293 cells. Biotinylation assay was performed and biotinylated proteins were immunoprecipitated using streptavidin-beads. After on beads-digestion, peptide fragments were analyzed by Orbitrap mass-spectrometry (MS). Furthermore, we cultivated primary dermal fibroblasts of three TMEM43 p.S358L carriers. Proteins were isolated from cell cultures and analyzed by MS. Additionally, TMEM43-p.S358L and control fibroblasts were investigated by transmission electron microscopy (TEM). Results: TurboID proteome data shows differences in the interacting proteome of TMEM43 WT and p.S358L. VDAC2, which is involved in metabolic regulation of lipids and part of the ER-mitochondrion contact site, was one of the prominent interacting proteins less represented in TMEM43 p.S358L. The proteome of fibroblasts show 11 proteins upregulated in TMEM43-p.S358L (p&lt;0.003). Of note, proteins involved in fatty acid metabolism, such as acyl-coenzym A thioesterase 1 encoded by the gene ACOT1, and Malonate-CoA ligase encoded by ACSF3 were strongly upregulated. ACOT1 and ACSF3 regulate intracellular levels of free fatty acids and are expressed in human cardiomyocytes. TEM images of TMEM43 p.S358L carriers show accumulation of multilamellar bodies, which may support the dysregulation of the lipid metabolism as a prominent pathomechanism. Conclusions: The altered interaction of TMEM43 p.S358L with VDAC2 is a plausible mechanism for miscommunication of ER and mitochondria perturbing the lipid homeostasis. Additionally, the differentially regulated proteins in dermal fibroblasts and the accumulation of multilamellar bodies also suggest a dysregulation of the lipid metabolism by TMEM43 p.S358L, which may explain the development of myocardial fibrofatty replacement contributing to ARVC5.
Abstract 12125: Ambulatory Pulmonary Artery Pressure-Guided Therapy in Patients With Chronic Heart Failure: A Systematic Review and Meta-Analysis
Authors: Angkawipa Trongtorsak, Sittinun Thangjui, Michael Dunleavy, Shengyuan Luo, Heba Osman, Vinh Chau, Karolina Marinescu, Anupama Rao, Annabelle Volgman, tisha suboc
Journal: Circulation (2022)

Background: In the past year, an implantable pulmonary artery pressure (PAP) sensor with CardioMEMS was approved by the FDA for heart failure (HF) patients with New York Heart Association (NYHA) class III or those with HF-related hospitalization (HFH). However, recent guidelines have not strongly recommended adding the PAP sensor to the standard of care in chronic HF patients. Objectives: We conducted this systematic review and meta-analysis to evaluate whether remote PAP-guided therapy can improve outcomes in chronic HF patients. Methods: We searched MEDLINE and Embase databases from inception to May 2022 to identify studies that compared outcomes of interest, including HFH and all-cause mortality in patients with HF who received remote PAP sensors in addition to the standard of care and those with the standard of care alone. Data from each study were combined using the random-effects model. Results: Four studies (2 randomized controlled trials and 2 matched cohort studies) with 7,505 patients (3,693 in the PAP sensor group and 3,812 in the control group) were included. The use of implantable PAP sensors in patients with chronic HF was associated with significantly lower HFH (hazard ratio (HR) = 0.76, 95% conference interval (CI) 0.68-0.84, p&lt;0.001) and all-cause mortality (HR=0.73, 95%CI 0.62-0.85, p&lt;0.001) as shown in Figure 1. Conclusions: Our meta-analysis demonstrated a significant reduction in HFH and mortality in HF patients with NYHA class III and remote PAP-guided therapy. Adding an ambulatory PAP sensor to the standard care may improve outcomes in chronic HF patients with NYHA class III.
Abstract 11292: Reducing Telemetry Utilization in Hospitalized Comfort Care Patients
Authors: Christine Park, Ramsey Kalil, Jihui Lee, Evan Sholle, Brock Daniels, Jennifer Lee
Journal: Circulation (2022)

Introduction: Telemetry overutilization increases costs and interventions that may result in patient harm, particularly at the end of life. ‘Comfort care’ (CC) patients are especially vulnerable to unnecessary telemetry use. Hypothesis: Using provider education and electronic medical record (EMR) modification, we anticipated a reduction in the use of telemetry in hospitalized CC patients at our institution by 25% compared to baseline. Methods: We included inpatient medicine house staff (HS) and physician assistants (PA) teams. We provided education only to HS (a total of 140 providers) on indications for telemetry and proper discontinuation of telemetry orders in the EMR. Subsequently, we modified the CC order set for all providers to simplify telemetry discontinuation in CC patients. We measured the rates of CC patients with active telemetry, correctly discontinued telemetry, and telemetry reordered after discontinuation over time. Results: From October 2020 to April 2022, the median number of CC patients with telemetry orders decreased from 16 to 8 monthly (Figure 1), and telemetry discontinuation improved by 54% on HS and 48% on PA services (Figure 2). HS discontinued telemetry sooner after CC orders were placed compared to PA. 93% of HS and 100% of PA discontinue telemetry orders were placed within 2 hours of CC orders in the intervention period. The rate of reordering telemetry after discontinuation remained unchanged at 4%. Conclusions: In hospitalized CC patients, provider education yielded earlier time to discontinuation of telemetry orders and reductions in telemetry use. EMR modification prompted substantial reductions in telemetry use among both HS and PA teams.
Abstract 11860: Poly-2-Methyl-2-Oxazoline as a Novel Mitigation Strategy in Bioprosthetic Heart Valves Affected by Calcification and Structural Degeneration in Patients With Metabolic Syndrome
Authors: Alexey Abramov, Yingfei Xue, Andrey Zakharchenko, Rajesh Soni, Jessica Tom, Vivian Moreno, Yuichi J Shimada, Robert LEVY, Giovanni Ferrari
Journal: Circulation (2022)

I: Bioprosthetic heart valves (BHV) engineered from glutaraldehyde-fixed bovine pericardium (GBP) are widely used for surgical and transcatheter interventions and affected by structural valve degeneration (SVD), often associated with calcification. Risk factors for accelerated SVD are under study. Susceptibility to oxidation, glycation and protein infiltration are key mechanisms. Here we characterize mechanisms of accelerated SVD in patients with metabolic syndrome (MetS) and propose a novel mitigation strategy with poly-2-methyl-2-oxazoline (POZ) coating. M: Retrospective chart review assessed risk factors for accelerated SVD. BHVs affected by SVD were selected (N=24) with/without MetS and next-generation proteomics with enrichment analysis (STRING-Db) performed. Unmodified (U) GBP and POZ GBP were incubated in serum from patients (N=128) with/without MetS to mimic protein absorption. U-GBP and POZ-GBP were subcutaneously implanted in Zucker Diabetic Fatty rats and controls. GBPs were analyzed with immunohistochemistry (IHC), differential scanning calorimetry (DSC), second-harmonic generation (SHG) and scanning electron microscopy (SEM). R: Kaplan Meier log-rank test (N = 251 patients) revealed patients with MetS were at increased risk of accelerated SVD (p = 0.004). Proteomics revealed (N=452) permanently incorporated proteins were differentially expressed (log2FC &gt;0.58, qvalue&lt;0.05) between MetS and nonMetS. Proteins involved in ECM remodeling and immune activation pathways were overrepresented (Fig 1). IHC, DSC, SHG and SEM results from revealed that POZ-GBP reduced protein infiltration, reduced calcification, and preserved structural integrity when compared to U-GBP. C: Accelerated SVD associated with MetS with calcification and serum protein accumulation is risk factor dependent and can be mitigated with POZ. This opens a possibility to chemically modify biomaterials for patients with this highly prevalent comorbidity.
Abstract 12401: Short-term Pdl-1 and Ctla-4 Blocking Agent Therapy Reduces Myocardial Pampk and Il-10 Levels, Increases Vascular Nf-kb Expression and Serum Il-1 / Il-6 Levels
Authors: Nicola Maurea, Claudia De Lorenzo, Margherita Passariello, Simona Buccolo, Annabella Di Mauro, Ciro Cipullo, Irma Bisceglia, Antonietta Caronna, Vincenzo Quagliariello
Journal: Circulation (2022)

Introduction: Several strategies based on immune checkpoint inhibitors (ICIs) have been developed or are under investigation for cancer therapy, opening to advantages in cancer outcomes. However, several ICIs-induced side effects emerged in these patients, especially a rare but clinically significant cardiotoxicity with high rate of mortality. Hypothesis: We analyzed the differential vasculo and cardiotoxicity of Pembrolizumab, Nivolumab and Ipilimumab in preclinical models highlighting on the molecular pathways involved. Methods: C57 female mice were treated with Ipilimumab, Pembrolizumab or Nivolumab (15 mg/kg) through intraperitoneal injection for 10 days. pAMPK expression and vascular p65/NF-kB was analyzed through Immunohistochemistry. Cardiac and systemic levels of IL-1α, IL-1β, IL-2, IL-6 and IL-10 were quantified through ELISA method Results: In preclinical models, all ICIs increased p65/NF-kB expression in vascular endothelial cells of mice compared to saline group. IHC analysis indicates that ICIs reduced pAMPK expression in myocardial cells. Notably, tissue levels of IL-1α, IL-1β, IL-2, IL-6 were strongly increased in ICIs group vs saline (p&lt;0.05 vs saline). On the other hand, levels of the anti-inflammatory cytokine IL-10 were strongly reduced ( overall reduction of 43.3-54.5 % vs saline) Conclusions: In preclinical models, a short treatment with ICIs is sufficient to confer a pro-inflammatory phenotype in the heart of mice. Furthermore, reductions in pAMPK indicate the inhibition of mitochondrial metabolism after ICIs. Furthermore ICIs induce chemokines involved in fibrosis, myocarditis and vascultitis. These results could indicate new therapeutic candidates aimed to prevent myocardial and vascular damages in cancer patients treated with ICIs